Previous studies have indicated that ethanol may affect styrene metabolism and toxicity in target tissues (e.g. brain). Morphological and biochemical changes have been reported in the respiratory tract of laboratory animals exposed to styrene either by inhalation or i.p. injection. The aim of the present study was, therefore, to investigate the influence of subchronic ethanol administration (5% in a Lieber-DeCarli liquid diet) on the morphological alterations of the respiratory tract induced by styrene inhalation (300 ppm, 6 h day(-1), 5 days a week for 2 weeks) in rats. Levels of reduced glutathione (GSH) in lung and liver tissues as well as in erythrocytes and whole blood were studied as indicators of overall GSH status, and urinary levels of the styrene metabolites-mandelic acid and phenylglyoxylic acid-were also measured as indicators of styrene-absorbed dose. Rats exposed to 300 ppm styrene presented morphological alterations throughout the respiratory tract. Electron microscopy analysis showed diffuse cell damage involving the tracheal, bronchiolar and alveolar epithelium. These abnormalities were accompanied by 40% depletion of GSH in the lung tissue and also 35% depletion in hepatic GSH in the absence of alteration of the GSH content in blood. Styrene metabolism was apparently induced by subchronic ethanol treatment, as indicated by an increased excretion of urinary mandelic (+140%, P < 0.05) and phenylglyoxylic (+50%) acids. However, repeated ethanol administration did not exacerbate the lung GSH depletion nor the damaging effect to the respiratory tract induced by the 2-week exposure to styrene alone. The lack of effects of ethanol on styrene pulmonary toxicity after combined exposure may be due to the different tissue distribution of the cytochrome P-450 isoforms involved in the styrene biotransformation to styrene-7,8-oxide, and their different induction by ethanol.

Administration, Oral↗

PubMedDate not supplied

3H-spiperone labels sigma receptors, not dopamine D2 receptors, in rat and human lymphocytes.

3H-Spiperone binds to dopamine D2 receptors in striatum and, under the assumption that it labels the same receptors in lymphocytes, this binding site has been suggested as a biological marker for schizophrenia. Recent studies, however, have raised questions about the existence of dopamine receptor changes in drug-free schizophrenic patients, as well as on the presence and/or dopaminergic nature of lymphocytic 3H-spiperone binding sites. In the present study we have conducted an investigation of the binding of 3H-spiperone to rat and human lymphocytes. We found that 3H-spiperone binds in a specific, saturable and reversible manner to a site in lymphocytes; however, its dissociation constant Kd (9 nM) is about 40-fold higher than in striatum. An extensive investigation of the 3H-spiperone sites indicated that their pharmacological profile was not that of a dopamine D2 site, but rather that of sigma receptors, a novel class of non-dopaminergic, non-opioid receptors which bind with high affinity antipsychotic drugs. Sigma receptors were also identified in lymphocytes using the specific ligand 3H-DTG (1,3-di-o-tolyl-guanidine), whose binding characteristics were comparable to those of sigma receptors in rat brain. Receptor density and the pharmacological profile of 3H-spiperone and 3H-DTG were similar. Both compounds also labelled a higher number of sites in B cells than in T cells and a good correlation was found between the lymphocytic binding of both ligands in a group of 58 people. These findings indicate that sigma receptors are present in lymphocytes and suggest that 3H-spiperone binding in these cells occurs to sigma sites and not to dopamine D2 sites.

Animals↗

PubMedDate not supplied

Propulsive motility of the guinea-pig colon after chronic lead treatment.

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Alanine↗